Our main goal is to learn how protein kinases and protein phosphatases recognize their three-dimensional protein substrates and how they cary out their respective catalytic reactions. We are primarily interested in defining how specificity is accomplished and how regulation of activity occurs. Our main focus will be the study of reactions in glycogen metabolism, phosphorylation and dephosphorylation of glycogen phosphorylase by phosphorylase kinase and protein phosphatase-1. Because of the multitude of important biological processes which are controlled by phosphorylation/dephosphorylation, we are convinced that understanding the molecular basis of glycogen phosphorylase interconversion reactions will provide a solid foundation for study of even more complex systems. Such information may lead to the design of inhibitors, mimics of protein structures, to combat abnormal phosphorylation reactions, e.g., in Alzheimer's disease. Our two specific aims are: 1) to determine the molecular basis by which phosphorylase kinase and protein phosphatase-1 recognize glycogen phosphorylase. Emphasis will be placed on the study of mutant forms of phosphorylase; 2) to define how the activities of the gamma catalytic subunit of phosphorylase kinase are controlled by the C-terminal region.